Chemistry and Metabolism of Amino Acids - 1 | Biochemistry - NEET PG PDF Download

Chemistry of Amino Acids

General Structure of Alpha Amino Acids

Structure: An alpha amino acid consists of:
A central alpha carbon (Cα) bonded to:

• A carboxyl group (-COOH)
• An amino group (-NH₂)
• A hydrogen atom
• A variable side chain (R group) specific to each amino acid

Non-Alpha Amino Acids

Definition: Amino acids where the amino group is not attached to the alpha carbon (e.g., beta, gamma, or other positions).

Example from PDF: Beta-Alanine(explicitly discussed on PAGE5 and PAGE6):

• A non-alpha amino acid with the amino group on the beta carbon.
• Sources:
  • Formed from degradation of cytosine and uracil.
  • Hydrolysis of beta-alanyl dipeptides.
• Found in:
  • Pantothenic Acid
  • Coenzyme A
  • Acyl Carrier Protein
  • Beta-Alanyl Dipeptides (e.g., Carnosine, Anserine)
• Note: Beta-alanine is highlighted as a "very important topic for national board pattern exams."
• Other Non-Alpha Amino Acids: Not explicitly listed in the PDF excerpt but implied in the context of beta-alanine’s unique structure compared to alpha amino acids.

Imino Acids

• Definition: Amino acids with a secondary amine group, where the nitrogen is part of a ring structure, technically making them imino acids.
• Example from PDF: Proline(explicitly classified as an imino acid on PAGE2):
  • Contains a pyrrolidine ring, where the alpha amino group is a secondary amine.
  • Classified as a nonpolar (hydrophobic) amino acid.
  • Special group: Pyrrolidine.
  • Note: Proline is unique due to its cyclic structure, affecting protein folding.
• Color Reaction: Proline gives a yellow color with ninhydrin (unlike the purple color of most alpha amino acids).

Classification of Amino Acids

Based on Chemical Structure

Branched Chain Amino Acids:

• Leucine, Isoleucine, Valine
• Mnemonic: LIV Amino Acids

Sulfur-Containing Amino Acids:

• Cysteine, Methionine

Amino Acids with Hydroxyl Group:

• Serine, Threonine

Amino Acids with Amide Group:

• Asparagine, Glutamine

Acidic Amino Acids:

• Aspartic Acid (Aspartate), Glutamic Acid (Glutamate)

Basic Amino Acids:

• Arginine (most basic), Lysine, Histidine

Aromatic Amino Acids:

• Phenylalanine, Tyrosine, Tryptophan, Histidine
• Notes:
  • Tryptophan and Histidine have heterocyclic aromatic rings (contain more than one atom type).
  • Tyrosine has a hydroxyl group.
  • Histidine has basic properties.

Imino Acid:

• Proline (explicitly noted as an imino acid).

Based on Side Chain Characteristics (Polarity)

Polar Amino Acids (Hydrophilic):

Charged:

• Acidic: Aspartic Acid, Glutamic Acid
• Basic: Histidine, Arginine, Lysine

Uncharged:

• Aliphatic with hydroxyl group: Serine, Threonine
• Aliphatic with amide group: Asparagine, Glutamine
• Simple: Glycine
• Sulfur-containing: Cysteine

Nonpolar Amino Acids (Hydrophobic):

• Simple: Alanine
• Sulfur-containing: Methionine
• Aromatic (except Histidine): Phenylalanine, Tyrosine, Tryptophan
• Branched Chain: Leucine, Isoleucine, Valine
• Imino Acid: Proline

Concepts:

• Learn polar and nonpolar amino acids by group classification.
• Mnemonic: ABC (Acidic and Basic are Charged).
• All branched chain amino acids are nonpolar.
• All aromatic amino acids except Histidine are nonpolar.

Based on Metabolic Fate

Ketogenic:

• Purely Ketogenic: Leucine
• Predominantly Ketogenic: Lysine

Both Glucogenic and Ketogenic:

• Phenylalanine, Isoleucine, Tyrosine, Tryptophan
• Mnemonic: LPITT (Lysine, Phenylalanine, Isoleucine, Tyrosine, Tryptophan)
• Glucogenic: All other amino acids not listed above.
• Concept: Learn ketogenic amino acids first, then those that are both glucogenic and ketogenic; the rest are glucogenic.

Based on Nutritional Requirement

Essential:

• Methionine, Threonine, Tryptophan, Valine, Isoleucine, Leucine, Phenylalanine, Lysine, Histidine
• Mnemonic: MeTT VIL PHLY

Semiessential:

• Arginine (required for growing children)

Nonessential:

• All other amino acids.

Special Groups Present in Amino Acids

Conservative (Homologous) Substitution
Definition: Replacement of an amino acid with another of similar characteristics.
Groups:

• Hydrophilic, Acidic: Aspartate, Glutamate
• Hydrophilic, Basic: Histidine, Arginine, Lysine
• Polar, Uncharged: Serine, Threonine, Glutamine, Asparagine
• Hydrophobic: Alanine, Phenylalanine, Leucine, Isoleucine, Valine

Nonconservative (Nonhomologous) Substitution

• Definition: Replacement of an amino acid with another of different characteristics.

Abbreviations of Amino Acids

• Unique First Letter:
  
• Non-Unique First Letter:
  
• Phonetic Abbreviations:
  
• Close to Initial Letter:
  

21st and 22nd Amino Acids

Selenocysteine:

• 21st amino acid, coded by UGA stop codon.
• Precursor: Serine, modified to cysteine with selenium replacing sulfur.
• Found in ~24 selenoproteins (e.g., Thioredoxin reductase, Glutathione peroxidase).

Pyrrolysine:

• 22nd amino acid, coded by UAG stop codon.
• Found in some archaea and bacteria.

Properties of Amino Acids

Optical Activity and Isomerism

• Chirality: Most amino acids have a chiral alpha carbon, forming L- and D-enantiomers.
• L-Isomers: Predominant in proteins.
• D-Amino Acids:
  • Free D-Aspartate, D-Serine (brain tissue).
  • D-Alanine, D-Glutamate (bacterial cell walls).
  • Bacillus subtilis: D-Methionine, D-Tyrosine, D-Leucine, D-Tryptophan.
  • Vibrio cholerae: D-Leucine, D-Methionine.
• Glycine: No chiral carbon, optically inactive.

Charge at Physiological pH (7.4)

• Carboxyl group: Negatively charged.
• Amino group: Positively charged.
• At pH > pI: Amino acid is negatively charged.

Potentially Toxic L-Amino Acids

UV Light Absorption

• Aromatic amino acids (Tryptophan, Phenylalanine, Tyrosine) absorb UV light (250–290 nm, max at 280 nm).
• Tryptophan has the highest absorption.

Decarboxylation of Amino Acids

• Process: Alpha decarboxylation forms biologic amines.
• Coenzyme: Pyridoxal Phosphate (PLP).
• Examples:
  

Color Reactions

• Biuret Test: Detects proteins (requires ≥ 2 peptide bonds).
• Ninhydrin Test: Detects alpha amino acids (purple complex, except Proline: yellow, Glutamine/Asparagine: brown).
• Other Tests:
  

Buffering Action

• Henderson-Hasselbalch: pH = pKa + log([Base]/[Acid]).
• pKa Ranges:
  
• Histidine has maximum buffering capacity at pH 7.4.

High-Yielding Facts

• Simplest: Glycine
• Most hydrophobic: Isoleucine
• Second most hydrophobic: Valine
• Most polar: Arginine
• Most abundant in proteins: Alanine
• Most abundant in plasma: Glutamine

Amino Acids as Neurotransmitters

• Glycine: Inhibitory (brainstem, spinal cord).
• Glutamate: Excitatory.
• Derivatives: Dopamine, Epinephrine, Norepinephrine, Serotonin, GABA.

Digestion of Proteins

• Endopeptidases: Pepsin, Trypsin, Chymotrypsin, Elastase.
• Exopeptidases: Carboxypeptidases, Aminopeptidases, Dipeptidases, Tripeptidases.
• Zymogen Activation: Pepsinogen → Pepsin; Trypsinogen → Trypsin (by enteropeptidase).

Biosynthesis of Urea (Urea Cycle)

• Site: Liver (mitochondria and cytoplasm).
• Reactions:
  1. Carbamoyl Phosphate Synthetase-I (CPS-I)
  2. Ornithine Transcarbamoylase (OTC)
  3. Argininosuccinate Synthetase
  4. Argininosuccinate Lyase
  5. Arginase
  6. N-Acetylglutamate Synthase
• Energetics: 4 high-energy phosphates, 3 ATPs directly.
• Urea Bicycle: Linked to TCA cycle via fumarate and aspartate.

Transamination

• Enzyme: Transaminase.
• Coenzyme: PLP.
• Examples: ALT (Alanine + α-Ketoglutarate → Pyruvate + Glutamate), AST (Aspartate + α-Ketoglutarate → Oxaloacetate + Glutamate).
• Exceptions: Proline, Hydroxyproline, Threonine, Lysine.

Oxidative Deamination

• Enzyme: Glutamate Dehydrogenase (GDH).
• Coenzymes: NAD⁺, NADP⁺.
• Minor Pathway: L-Amino Acid Oxidase (FMN, H₂O₂).

Nonoxidative Deamination

• Dehydrases (Serine, Threonine), Histidase (Histidine), Desulfhydrases (Cysteine, Homocysteine).

Transdeamination

• Transamination + Oxidative Deamination.

Transport of Ammonia

• From Tissues/Brain: As glutamine (Glutamine Synthetase).
• From Skeletal Muscle: As alanine.

Urea Cycle Disorders

Disorders:

• Hyperammonemia Type I (CPS-I)
• Hyperammonemia Type II (OTC, most common, X-linked)
• Citrullinemia Type I
• Arginosuccinic Aciduria
• Hyperargininemia
• Citrullinemia Type II (Citrin)
• HHH Syndrome (Ornithine Transporter)

Biochemical Investigation

• Ammonia: Berthelot, Glutamate Dehydrogenase, Electrodes.
• Urea: Diacetyl Monoxime, Urease.
• Tool: Tandem Mass Spectrometry.

Treatment

• Arginine: Provides ornithine, contraindicated in arginase deficiency.
• Acylation: Sodium Benzoate (hippuric acid), Sodium Phenylacetate (phenylacetylglutamine).

Individual Amino Acid Metabolism

Phenylalanine

• Aromatic, essential, hydrophobic, partly glucogenic/ketogenic.

Tyrosine

• Aromatic, nonessential, partly glucogenic/ketogenic.

Synthesis of Tyrosine

• Enzyme: Phenylalanine Hydroxylase (monooxygenase, tetrahydrobiopterin, NADPH).

Catabolism of Tyrosine

• Pathway:
  • Tyrosine → p-Hydroxyphenylpyruvate → Homogentisate → Maleylacetoacetate → Fumarylacetoacetate → Fumarate + Acetoacetate.
• Enzymes: Tyrosine Transaminase, p-Hydroxyphenylpyruvate Hydroxylase, Homogentisate Oxidase, Maleylacetoacetate Isomerase, Fumarylacetoacetate Hydrolase.

Specialized Products

• Melanin, Catecholamines, Thyroxine.